The application of widely differing scientific disciplines to biological research has yielded profound advances in the ways that biological systems are characterized and monitored, and the way in which biological disorders are treated. In particular, the combination of solid state electronics technologies to biological research applications has provided a number of important advances including, e.g., molecular array technology, i.e., DNA arrays (See, U.S. Pat. No. 6,261,776), microfluidic chip technologies (See. U.S. Pat. No. 5,976,336), chemically sensitive field effect transistors (ChemFETs), and other valuable sensor technologies.
Zero mode waveguide (ZMW) technology provides vet another extension of these semiconductor fabrication technologies to different areas of research and diagnostics. In particular, ZMW arrays have been applied in a range of biochemical analyses and particularly in the field of genetic analysis. ZMWs typically comprise a nanoscale core, well or opening disposed in an opaque cladding layer that is disposed upon a transparent substrate. Due to the narrow dimensions of the core electromagnetic radiation that is of a frequency above a particular cut-off frequency will be prevented from propagating all the way through the core. Notwithstanding the foregoing, the radiation will penetrate a limited distance into the core, providing a very small illuminated volume within the core. By illuminating a very small volume, one can potentially interrogate very small quantities of reagents, including, e.g., single molecule reactions.
By monitoring reactions at the single molecule level, one can precisely identify and/or monitor a given reaction. This is the basis behind a particularly promising held of single molecule DNA sequencing technology that monitors the molecule by molecule synthesis of a DNA strand in a template dependant fashion by a single polymerase enzyme.
Despite the foregoing advances, a number of additional improvements and advances are available. The present invention provides a number of such advances and improvements.